ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective:To discuss whether safranal affects the proliferation,migration,and phenotypic transformation of the vascular smooth muscle cells(VSMCs)in a high-glucose environment and to clarify the function of safranal in the prevention and treatment of diabetic(DM)vascular complications.Methods:The SD rats were selected as experimental subjects;primary VSMCs were cultured from rat thoracic aortas and divided into control group,25 mmol·L-1 high glucose(HG)group,HG+20 μmol·L-1 safranal group,HG+40 μmol·L-1 safranal group,and HG+80 μmol·L-1 safranal group.The cells in control group received no treatment;the cells in 25 mmol·L-1 HG group were pretreated with 25 mmol·L-1 HG;the cells in HG+20,40,and 80 μmol·L-1 safranal groups were further treated with 20,40,and 80 μmol·L-1 safranal respectively for 48 h on the basis of 25 mmol·L-1 HG group.Cell counting kit-8(CCK-8)method was used to determine the appropriate concentration of safranal and detect the viabilities of the VSMCs in various groups;cell scratch healing assay was used to detect the scratch healing rates of the VSMCs in various groups;Transwell chamber assay was used to detect the numbers of the migration VSMCs in various groups;immunofluorescence method was used to detect the fluorescence intensities of alpha-smooth muscle actin(α-SMA)and rabbit anti-osteopontin(OPN)in the VSMCs in various groups;Western blotting method was used to detect the expression levels of OPN,α-SMA,and proliferating cell nuclear antigen(PCNA)in the VSMCs in various groups.Results:Under microscope,on the 4th day of in vitro culture,the spindle-shaped or triangular cells crawled out from the edge of the thoracic aorta tissue blocks,with long spindle being the most common morphology.On the 14th,the cells gradually covered the bottom of the dish;when cell density reached 80%-90%,the characteristic"hills and valleys"growth pattern appeared.Third-generation cells were taken for immunofluorescence identification;immunofluorescence staining with VSMC-specific marker α-SMA showed positive expression of α-SMA protein in the primarily cultured VSMCs.The CCK-8 assay results showed that compared with control group,the cell viability of the cells in 160 μmol·L-1 safranal group was significantly decreased(P<0.01),indicating toxic damage to the cells.Under the conditions of safranal concentrations at 20,40,and 80 μmol·L-1 respectively,after 48 h intervention on VSMCs,no significant adverse effect on cell viability was observed;considering both the effect and toxicity of safranal,these three concentrations were used in subsequent cell experiments.After 48 h intervention,compared with control group,the activity of the VSMCs in 25 mmol·L-1 HG group was increased(P<0.001);compared with 25 mmol·L-1 HG group,the activities of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05).The cell scratch healing assay and Transwell assay results showed that after 48 h intervention,the scratch healing rate of the VSMCs in 25 mmol·L-1 HG group was significantly higher than that in control group(P<0.01),and the number of transmembrane cells through the Transwell chamber was significantly increased(P<0.05);compared with 25 mmol·L-1 HG group,the scratch healing rates of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05),and the number of transmembrane cells was decreased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was significantly weakened(P<0.001),while the fluorescence intensity of OPN protein was significantly enhanced(P<0.001);compared with 25 mmol·L-1 HG group,the fluorescence intensities of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually increased(P<0.05),and the fluorescence intensities of OPN were gradually weakened(P<0.05).The Western blotting method results showed that compared with control group,the expression level of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was decreased(P<0.05),and the expression levels of PCNA and OPN proteins were increased(P<0.01);compared with 25 mmol·L-1 HG group,the expression level of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were increased(P<0.05),and the expression levels of PCNA and OPN proteins were decreased(P<0.05).Conclusion:Safranal can inhibit the proliferation,migration,and phenotypic transformation of the VSMCs induced by high glucose.

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of apixaban in the prevention and treatment of cancer-associated venous thromboembolism （CA-VTE）， and provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， the Cochrane Library， CNKI， Wanfang， VIP database and other websites of health technology assessment （HTA）， systematic review/meta-analysis， pharmacoeconomic studies and HTA reports of apixaban in the prevention and treatment of CA-VTE were collected. After data extraction and quality evaluation， the results of the included study were analyzed descriptively. RESULTS A total of 23 literatures were included， involving 16 systematic review/meta-analysis and 7 pharmacoeconomic studies. In terms of efficacy， compared with placebo， prophylactic use of apixaban could significantly reduce the incidence of venous thromboembolism （VTE） in outpatient adult cancer patients receiving chemotherapy （P＜0.05）. Compared with low-molecular weight heparin （LMWH）， rivaroxaban and warfarin， there were no statistically significant differences in the incidence of VTE for apixaban （P＞0.05）； nevertheless， apixaban was ranked as the most preferable choice. For the treatment of patients with CA-VTE， compared with warfarin， apixaban could significantly reduce the recurrence rate of VTE （P＜0.05）. While compared with patients treated with LMWH， rivaroxaban， edoxaban and dabigatran， there were no statistically significant differences in the recurrence rates of VTE， deep venous thrombosis and pulmonary embolism among patients using apixaban （P＞0.05）. In terms of safety， compared with placebo， prophylactic use of apixaban showed a higher occurrence of major bleeding in outpatient adult cancer patients receiving chemotherapy （P＜0.05）， while compared withpatients treated with LMWH， rivaroxaban， and warfarin， there were no statistically significant differences in the incidence of major bleeding among patients using apixaban （P＞0.05）； despite this， apixaban was ranked as the most favorable option. For the treatment of patients with CA-VTE， compared with dalteparin， the incidence of major bleeding and all-cause mortality of apixaban were similar （P＞0.05）， while the incidence of clinically relevant non-major bleeding （CRNMB） was higher （P＜0.05）. Compared with edoxaban， the incidence of major bleeding of apixaban was reduced significantly （P＜0.05）， while there was no significant difference in the incidence of CRNMB， the incidence of clinically relevant bleeding and all-cause mortality （P＞0.05）. Compared with rivaroxaban， warfarin and dabigatran， there were no significant differences in the incidence of major bleeding， the incidence of CRNMB， the incidence of clinically relevant bleeding and all-cause mortality （P＞0.05）. In terms of cost-effectiveness， the researches in China showed that apixaban was cost-effective in preventing CA-VTE； foreign studies showed that apixaban was cost-effective in preventing and treating CA-VTE. CONCLUSIONS Apixaban is effective， safe and cost- effective in the prevention and treatment of CA-VTE.

Objective To investigate the effects of saikosaponin D(SSD)on the growth of esophageal squamous cell carcinoma(ESCC)Eca109 cells and the hypoxia-inducible transcription factor-2α(HIF-2α)/nuclear factor-κB p65(NF-κB p65)pathway.Methods Different concentrations of SSD(0,3,6,9,12,15,18,21,24 μmol·L-1)were used to treat Het-1a normal esophageal squamous epithelial cells and Eca109 ESCC cells to screen the experimental concentration of SSD.Eca109 cells were separated into control(NC)group,HIF-2α inhibitor(PT2385)group,SSD low and high concentration(SSD-L,SSD-H)groups,SSD-H+empty lentivirus(LV-NC)group,and SSD-H+HIF-2α recombinant lentivirus(LV-HIF-2α)group.MTT assay was applied to detect cell viability.Flow cytometry was applied to detect cell apoptosis.ELISA was applied to detect the levels of TNF-α,IL-1β,and IL-8 in cell culture media.Western blot was applied to detect cell proliferation,apoptosis,and protein expression related to the HIF-2α/NF-κB p65 pathway.The Eca109 cell tumor bearing nude mouse model was established to verify the effect of SSD on the in vivo growth of Eca109 cells.Results 6 and 12 μmol·L-1 SSD were selected as experimental concentrations.Compared with the NC group,the cell viability,TNF-α,IL-1β,IL-8 levels in cell culture medium,PCNA,Bcl-2,HIF-2α,p-NF-κB p65/NF-κB p65 protein levels,subcutaneous transplant tumor volume and weight in nude mice,serum TNF-α,IL-1β,IL-8 levels,and positive expression of HIF-2α and NF-κB p65 proteins in the PT2385 group,SSD-L group,and SSD-H group were lower,the apoptosis rate,Bax,and Cleaved-caspase3 protein levels were higher(P<0.05 or P<0.01).Overexpression of HIF-2α prominently weakened the inhibitory effects of SSD on the proliferation of Eca109 cells and the growth of subcutaneous transplanted tumors in nude mice(P<0.05 or P<0.01).Conclusion SSD can inhibit the proliferation of Eca109 cells,induce cell apoptosis,and suppress the growth of subcutaneous transplanted tumors of Eca109 cells in nude mice.Its effect may be related to the inhibition of the activation of the HIF-2α/NF-κB p65 pathway.

Objective:To analyze the efficacy of different doses of esketamine in maintaining general anesthesia in elderly patients undergoing radical resection of esophageal cancer.Methods:A total of 98 elderly patients who underwent radical resection of esophageal cancer and admitted from Jun. 2023 to May. 2025 in Shangqiu First People’s Hospital were selected and divided into Group A ( n=50, 0.25 mg·kg -1·h -1) and Group B ( n=48,0.5 mg·kg -1·h -1) according to the dose of esketamine. The following situations between the two groups were compared: (1) hemodynamics [mean arterial pressure (MAP), heart rate (HR) ] before anesthesia induction (T0), 30 minutes after the start of the operation (T1), and at extubation (T2) ; (2) Stress inflammatory indicators [norepinephrine (NE), C-reactive protein (CRP) ] before the operation and 1 day after the operation; (3) Analgesia status [Dosage of propofol and remifentanil, remedial analgesia rate, and the degree of analgesia was evaluated by visual analogue scale (VAS) 2 hours after the operation]; (4) Postoperative recovery [postoperative eye-opening time, extubation time, anesthesia recovery time, and postoperative recovery quality was evaluated using the Chinese version of the 15-item Quality of Recovery (QoR-15) Scale 1 day after the operation]; (5) Safety. Results:(1) At time T1, MAP of both groups was lower than that at time T0,and at time T2, MAP of group B was higher than that at time T1 ( P<0.05). At times T1 and T2, HR of both groups was lower than that at time T0, and HR of both groups at time T2 was higher than that at time T1 ( P<0.05). At time T1, MAP and HR in group B were lower than those in group A ( P<0.05). (2) The dosages of propofol and remifentanil in group B were lower ( P<0.05) ,while the comparison of remedial analgesia rate and VAS score between the two groups showed P>0.05. (3) One day after the operation,the levels of serum NE and CRP in both groups were higher than those before the operation,while those in group B were even lower ( P<0.05). (4) The incidence of adverse reactions in group B (20.83%) was slightly higher than that in group A (10.00%). (5) The eye-opening time,extubation time and anesthesia recovery time after surgery in group B were all longer than those in group A ( P<0.05), while the comparison of QoR-15 scores between the two groups showed P>0.05. Conclusions:In the maintenance of general anesthesia for elderly patients undergoing radical resection of esophageal cancer, the intraoperative hemodynamic fluctuations of low-dose esketamine are smaller. Although the dosages of propofol and remifentanil are higher and the postoperative recovery time is longer, there are no significant differences in analgesic effect, adverse reactions or recovery quality, while the stress and inflammatory responses of high-dose esketamine are smaller.

Acute large vessel occlusion stroke(ALVOS)of anterior circulation is associated with severe clinical manifestations and high rates of disability and mortality.Mechanical thrombectomy has emerged as the primary therapeutic intervention.However,post-procedural outcomes remain highly variable,and patients continue to face elevated risks of poor prognosis.Machine learning,a transformative tool in medical research,enables comprehensive analysis of multimodal data to identify specific biomarkers and improve the accuracy of predictions for clinical outcomes and adverse events.This review summarized the latest developments in machine learning applications aim at predicting post-thrombectomy prognosis and risk of adverse event,including futile recanalization,hemorrhagic transformation,and malignant cerebral edema in patients with anterior circulation ALVOS in order to provide a basis for developing personalized treatment plan and improve their clinical prognosis.

Objective:To fine-tune the mT5 (massively multilingual pre-trained text-to-text transformer) large language model, automatically generate report conclusions for teaching purposes from chest CT image descriptions, and assess the quality of automatically generated conclusions.Methods:The training set included 3 000 high-quality physical examination chest CT reports from one hospital, and the external validation set consisted of 600 physical examination chest CT reports from two other hospitals. Experienced radiology teaching physicians assessed the consistency between the generated conclusions and the original physician-written conclusions in the external validation set using a 5-point Likert scale across five linguistic indicators (correctness of examination information, correctness of lesion detection, standardization of terminology, applicability of the conclusions, and simplicity of conclusions). Using the original report conclusions as the reference, the accuracy of the conclusions generated based on the external validation set in describing four major thoracic conditions (pulmonary nodules, pneumonia, emphysema, pleural effusion) was evaluated. Perform chi square test using SPSS 25.0.Results:In the external validation set, the mean consistency score between the generated conclusions and the original conclusions given by the radiology teaching physicians was >4 points, indicating agreement with the original conclusions. In the generated conclusions, the description of the four major thoracic conditions demonstrated 0.95-1.00 (95% CI=0.91-1.00) accuracy, 0.76-1.00 (95% CI=0.59-1.00) sensitivity, and 0.97-1.00 (95% CI=0.91-1.00) specificity. Conclusions:The chest CT report conclusion generation system based on the mT5 large language model demonstrated high accuracy and is expected to provide immediate and efficient automated guidance for standardized residency training.